|Publication number||US5925030 A|
|Application number||US 08/793,497|
|Publication date||Jul 20, 1999|
|Filing date||Aug 4, 1995|
|Priority date||Aug 15, 1994|
|Also published as||CA2197170A1, DE69519035D1, DE69519035T2, EP0776228A1, EP0776228B1, WO1996004953A1|
|Publication number||08793497, 793497, PCT/1995/39, PCT/IE/1995/000039, PCT/IE/1995/00039, PCT/IE/95/000039, PCT/IE/95/00039, PCT/IE1995/000039, PCT/IE1995/00039, PCT/IE1995000039, PCT/IE199500039, PCT/IE95/000039, PCT/IE95/00039, PCT/IE95000039, PCT/IE9500039, US 5925030 A, US 5925030A, US-A-5925030, US5925030 A, US5925030A|
|Inventors||Joseph Gross, John Gerard Kelly|
|Original Assignee||Elan Corporation, Plc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (21), Referenced by (137), Classifications (15), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This invention relates to an orally administrable delivery device which is especially suited for the delivery of an active ingredient such as a drug to the gastrointestinal tract.
Various types of devices are known for the delivery of active ingredients in a controlled manner to the gastrointestinal tract for absorption into the systemic circulation so as to maximise the efficacy of such active ingredients.
Our International Publication WO 94/01165 describes and claims a medication administering device which comprises a housing of a size enabling it to be introduced into a body cavity. The housing, which is of a material insoluble in body cavity fluids, but which is provided with an opening, is divided into first and second expansible and contractible chambers by a displaceable member. The second chamber includes electrically-controlled means for generating a gas to expand said chamber and force medication contained in the first chamber out through the opening into the body cavity and thus is based on electrolytic technology. The device of our International Publication WO 94/01165 is an example of what is referred to as a "smart" pill.
A "smart" pill is described briefly in Popular Science, May 1992, at page 25. The "smart" pill in question is in the form of a capsule containing a tiny radio transmitter that transmits a continuous signal as it passes through the body so as to enable its location in the body to be detected at any given time. When it reaches a predetermined location, a computer signals the pill to release the medication contained therein by actuating a piston within the capsule to force out medication contained within a chamber in the capsule.
The device of our International Publication WO 94/01165 includes, in certain embodiments, an electrolytic cell and a small battery with associated electronics. In other embodiments, however, the power source is derived from two fine wires of diverse metals wrapped around the exterior surface of the housing. The two wires, in combination with the gastric fluids in which they are immersed and by which they are separated, act as a voltaic cell which is used as the power source for an electrolytic cell within the second chamber.
Thus, although the requirement for a battery is obviated, there are certain drawbacks associated with this method of generating a gas within the second chamber.
Firstly, it is not always possible to achieve the desired rates of gas generation, since the rate of gas generation is directly dependent upon the current passing through the electrolytic cell. This current depends in turn, upon the resistance provided by the electrolytic cell and the magnitude of voltage generated by the voltaic cell on the external surface of the housing. The voltage generated is not always sufficient to drive the electrolytic cell at the desired rate.
Secondly, it is undesirable to use the gastric fluids as the electrolyte for a battery, since the chemical reactions occurring at the electrodes may lead to undesirable products (such as metallic compounds or gases) being created within and released into the gastrointestinal tract.
Thus, it is an object of the present invention to overcome the problems indicated above and to provide a device which is structurally more simple, which is cheaper and easier to manufacture, and which is more compact and more efficient than the devices of the prior art.
The invention provides such a device which is an orally administrable delivery device comprising a housing with walls of a water permeable material and having at least two chambers: a first chamber adapted to receive an active ingredient and which is provided with an orifice through which the active ingredient is expelled under pressure in a liquid form; and a second chamber containing at least one of two spaced-apart electrodes which form part of an electric circuit which is closed by ingress of an aqueous ionic solution into said second chamber, such that a potential difference is set up between the electrodes and a current flows through said circuit resulting in the generation of a gas at said at least one electrode, and the gas once generated acting on a displaceable membrane to compress the first chamber and expel the active ingredient through the orifice for progressive delivery to the gastrointestinal tract.
The water-permeable material of which the walls are made allow water to enter the chamber substantially immediately, remaining intact throughout the delivery of the active ingredient. Thus, the rate of delivery depends on the electric circuit which generates the gas and not on the rate at which water is permitted to enter the housing. Suitable water-permeable materials are also referred to as hydrophilic materials.
The device according to the invention in its simplest form achieves release of active ingredient to the gastrointestinal tract in a controlled manner similar to that achieved with controlled release multi-particulate formulations and other controlled release oral dosage forms.
The active ingredient which is expelled from the device in a liquid form is immediately available for absorption by the gastrointestinal tract with the attendant advantages, if required. However, the device according to the invention by appropriate selection of the materials of the device and the construction thereof can also be used to achieve delivery of an active ingredient so as to achieve a therapeutic effect over a 24 hour period, if required.
The second chamber preferably contains a pair of spaced-apart electrodes.
However one electrode may be situated outside the housing with the current flowing by ionic transport through the aqueous solution connecting the electrodes through the walls of the housing.
Preferably, the electrodes represent an anode and a cathode, the sum of the half-cell reactions of which is positive and wherein at least one of the electrode reactions produces a gas when said electric circuit is closed.
The anode and cathode can each be in the form of a rod, a sheet, a deposited layer or a compressed powder.
The anode and the cathode will be made from bio-compatible materials such as platinum, nickel and silver. For example, one can use a nickel metal anode and a silver chloride cathode. At the nickel cathode, water is converted to oxygen gas and at the silver chloride cathode, the silver chloride is converted to silver metal and chloride ions.
Preferably, the electrodes are connected by a connection which is isolated from the electrolyte. Thus, the electric circuit follows a path from the anode, through the electrolyte to the cathode, and back to the anode via a connection which is isolated from the electrolyte.
Further preferably, the connection is external of the second chamber.
Suitably, the electric circuit includes a micro-processor for controlling the generation of gas. The rate of gas generation depends directly on the magnitude of the current passing through the electrolyte. Thus, by controlling the current, the micro-processor controls the generation of gas.
The rate and amount of gas generation is a function which is controlled by the electric circuit, such as by varying the current over time or by breaking the circuit, and thus stopping the generation of gas, for certain periods of time.
It will be appreciated that a range of fully controllable devices can be provided by constructing them with different electronic units.
Once the device is swallowed, the water permeable housing begins to absorb liquid from the gastrointestinal tract and liquid enters both the first and second chambers. Gas generation commences and simultaneously provides the power necessary to power the electrolytic reaction.
Furthermore, the electric circuit can include a sensor for sensing a condition in the body and can control the generation of gas in response to the output of said sensor.
For example, the sensor may be or include any one or more of the following: a pH sensor, to effect the delivery of the active ingredient to a predetermined region of the gastrointestinal tract; a temperature sensor to control the delivery of the active ingredient in response to body temperature; or a sound sensor, such as a microphone, to control the delivery of the active ingredient in response to the pulse rate.
Such biosensors can provide a feedback to the electric circuit.
In an alternative embodiment the device is equipped with a radio receiver which communicates with the electric circuit such that delivery of the active ingredient can be controlled by providing radio signals from outside the body. A transmitter can also be provided to transmit information relating to the operation of the device or its location in the gastrointestinal tract for example.
The displaceable membrane is preferably made of a flexible material such as polyvinyl chloride or a silicone rubber.
The electrode(s) can be coated on a surface of the second chamber.
The coating of the electrode(s) can be effected by employing such techniques as sputtering, evaporation, the use of compressed powders, printing and the like.
The material of the walls of the device is suitably a non-toxic material which is selected from natural and synthetic materials.
Such materials include plastics materials, cellulose or cellulose derivatives, including paper, or a biodegradable material such as starch. Generally such materials are gas permeable when dry, but gas impermeable when absorbing liquid through the pores or channels in the structure thereof, since the liquid effectively "blocks" the pores.
In the case of the embodiments referred to above, the gas is produced at an accurate rate without the need for a conventional battery.
It will be appreciated that the device in accordance with the invention has substantial advantages when compared with existing micro-encapsulated pills or the so-called "osmotic" pill, primarily in that the "osmotic" pill has a delivery rate which cannot be controlled, but which is predetermined by the structure of the pill. In certain embodiments of the present invention, however, the delivery of the drug can be controlled as precisely as available electronics will allow, and in response to virtually any chosen conditions.
Accordingly, the underlying principle in the case of the device according to the invention is that the electrochemical cell produces gas via spontaneous reactions without the need for an external power source. In essence, the second chamber behaves like a battery; in this case, the product of the reaction is a gas. In order for the cell in the second chamber to operate effectively, the anode and cathode materials must be chosen so that the individual reactions at the anode and cathode together result in a total cell reaction which is spontaneous. The total cell reaction is the sum of the individual anode and cathode reactions. Each reaction is characterised by its half-cell potential which is a known thermodynamic quantity. The half-cell potentials of many reactions are listed in standard reference books. In order for the total cell reaction to be positive (spontaneous), the sum of the anode and cathode half-cell reactions must be positive.
Representative examples of different types of cells which may be accommodated in the second chamber are as follows:
Anode material: Nickel, platinum, carbon or graphite.
Anode form: Rods, sheets or deposited layers.
Anode reaction to produce oxygen:
______________________________________ Half-Cell Potential______________________________________2H2 O → O2 + 4H+ + 4e- -1.229______________________________________
In order for the total cell reaction to be spontaneous the cathode half-cell reaction must have a positive value greater than +1.229.
______________________________________ Half-Cell Potential______________________________________Bi2 O4 + 4H+ + 2e- → 2BiO + 2H2 1.59NiO2 + 4H+ + 2e- → Ni+2 + 2H2 1.68PbO2 + 4H+ + 2e- → Pb+2 + 2H2 1.455______________________________________
The above cathodes are suitably in the form of deposited layers or compressed powders.
Cathode material: Nickel, platinum, carbon or graphite.
Cathode form: Rods, sheets, or deposited layers.
Cathode reaction to produce hydrogen gas:
______________________________________ Half-Cell Potential______________________________________2H+ + 2e- → H2 0.0______________________________________
In order for the total cell reaction to be spontaneous the anode half-cell reaction must have a positive half-cell potential greater than 0.
______________________________________ Half-Cell Potential______________________________________Al → Al+ +1.66-Ba → Ba+2 + 2e- +2.90B + 3H2 O → H3 BO3 + 3H+ + 3e- +0.87Cr → Cr+3 + 3e- +0.74Fe → Fe+2 + 2e- +0.49In → In+3 + 3e- +.342Ni → Ni+2 + 2e- +.250Pb → Pb+2 + 2e- +.126Sn → Sn+2 + 2e- +.1502Ta + 5H2 O → Ta2 O5 + 10H+ + 10e- +0.81Ti → Ti+2 + 2e- +1.63Ti + H2 O → TiO+2 + 2H+ + 4e- +0.89______________________________________
The above anodes are suitably in the form of rods, sheets, or deposited layers.
Similar reactions can occur at basic pH levels. For instance, to produce oxygen at the anode
______________________________________ Half-Cell Potential______________________________________40H- → O2 + 2H2 O + 4e- -.401______________________________________
at a platinum, nickel, carbon or graphite electrode. The corresponding cathode reactions can be chosen from:
______________________________________ Half-Cell Potential______________________________________2AgO + 2OH- → Ag2 O3 + H2 O +.74-MnO2 + 4OH- → MnO4 -2 + 2H2 O +2e- +.60______________________________________
The above cathodes are suitably in the form of rods or compressed powders of silver oxide or manganese dioxide.
The orifice is suitably of the order of 0.1 mm or less and is suitably achieved by laser drilling.
The gas once generated cannot escape from the second chamber. It will be appreciated that such gas will be at a relatively low pressure and that the capillary forces generated by the ingress of water will be greater than the pressure of the gas generated, so that the gas will be confined to the second chamber and will cause the displaceable membrane to be displaced, thereby contracting the first chamber and expelling the active ingredient through the orifice.
It will be appreciated also that the orifice provides the path of least resistance for the liquid containing the active ingredient, which will exit the first chamber through the orifice.
The orifice can be initially closed by a material which is soluble in the liquid environment of the gastrointestinal tract.
Accordingly, the material can be gelatinous material or other material used in capsules which is soluble in body fluids.
The gas generation rate builds up slowly, for example for a period of approximately 10 minutes, and thereafter reaches a steady state, unless the electric circuit is adapted to vary the current flowing therethrough.
The device according to the invention will preferably be the size of a regular pill or capsule.
The active ingredient is preferably solid, more particularly a solid in powder form. However, depending on the shelf-life of the active ingredient in liquid form, it is also possible for the active ingredient to already be in a liquid or a semi-solid form in the first chamber at the time of administration of the device.
Suitable active ingredients for administration using the device according to the invention are: peptides, proteins, hormones, including peptide and protein hormones, prostaglandins, analgesics, anti-migraine agents, sedatives, narcotic antagonists, anti-coagulants, anti-emetic agents, anti-infective agents, anti-diabetic agents, cardiovascular agents, anti-hypertensive agents, chelating agents, anti-anginal agents, anti-duretic agents, chemotherapeutic agents and anti-neoplastics.
The device will be further illustrated by the following description of an embodiment thereof, given by way of example only with reference to the accompanying Drawings in which:
FIG. 1 is a cross section of an embodiment of a device according to the invention;
FIG. 2 is an enlarged view of a detail taken from FIG. 1; and
FIG. 3 is a perspective view of a cut away section of the device illustrated in FIG. 2.
In FIG. 1, there is illustrated, generally at 10, an orally administrable delivery device according to the invention. The device 10 has a housing 11, the walls of which are formed from starch which is water permeable due to its inherent porosity and through which water and entrained solutes are drawn by capillary action. A membrane 12 within housing 11 defines, on one side thereof, a drug delivery chamber 13 and, on the other side thereof, a gas generation chamber 14. The generation of a gas within gas generation chamber 14 as hereinafter described increases the pressure therein and tends to push membrane 12, which is freely displaceable, upwards so as to reduce the volume of drug delivery chamber 13. The housing 11 is provided with an orifice 15 though which a drug-containing liquid is expelled when drug delivery chamber 13 is contracted. Although gas generation chamber 14 is initially air filled, the capillary pressure tending to draw the liquid into the gas generation chamber 14 is stronger than the resistive gas pressure which tends to oppose the entry of solution into the chamber 14.
When the device 10 is swallowed, liquid from the aqueous environment of the gastrointestinal tract permeates through the hydrophilic starch walls of housing 11 due to the capillary pressure related to the hydrophilic material used. Admission of water into drug delivery chamber 13 causes the drug contained therein (not shown) to be dissolved or suspended in the gastrointestinal fluid, as the case may be.
The drug delivery chamber 13 is initially filled with the drug to be delivered in the form of a powder. Since the walls of the drug delivery chamber 13 are made of hydrophilic material, liquid is admitted into the drug delivery chamber 13 in the same manner as it is admitted into the gas generation chamber 14. If the drug is soluble in water, then the drug is dissolved when the liquid enters the drug delivery chamber 13.
If the drug is water insoluble, a fine powder of the drug will nevertheless form a suspension in the liquid. Thus, the same principles apply as previously described, and the expansion of the gas generation chamber 14 results in the contraction of the drug delivery chamber 13 and the expulsion of the drug-containing liquid (this time in the form of a suspension) from the device 10 to the gastrointestinal tract.
The gas generation chamber 14 contains two electrodes 16,17. Electrode 16 is a nickel metal element and electrode 17 is a silver chloride element.
Referring additionally to FIG. 2, wherein there is shown a detail of the device of FIG. 1 in an enlarged view, it can be seen that electrodes 16 and 17 are physically isolated from one another but are electrically connected to one another via electrical conductors 18 and a printed circuit 19. The printed circuit 19 is produced as a metallization pattern on an insulating substrate 20.
When an ionic solution bridges the gap between the electrodes 16,17, a circuit is completed. The circuit comprises the electrodes 16,17, the electrical conductors 18, the printed circuit 19 and the ionic solution within chamber 14. When the circuit is completed, a potential difference is set up as a result of the differing half-cell potentials of the two electrodes in solution. This difference in potential leads to the flow of a current through the circuit which results in an electrochemical reaction occurring at the nickel and silver chloride electrodes which are immersed in the solution and connected electrically. At the nickel anode, water is converted to oxygen gas, and at the silver chloride cathode, the silver chloride is converted to silver metal and chloride ions. The reaction of the electrodes with the electrolyte results in gas being generated at the nickel electrode.
Since the printed circuit 19 forms part of the electric circuit, it can be used to control the current flowing through the circuit, and thereby control the rate of generation of gas within gas generation chamber 14. In the embodiment illustrated a pH sensor 21 acts as an input to circuit 19. An insulating plastics layer 22 separates the printed circuit 19 from the external environment, so that the circuit 19 is electrically isolated therefrom, but the pH sensor 21 is immersed in the gastrointestinal fluid surrounding the device 10.
At very low pH levels, gas generation is inhibited by printed circuit 19. In higher pH environments, printed circuit 19 allows the current to flow more freely. Thus, the device illustrated is designed to withhold drug delivery within the stomach (a very low pH environment), and to increase delivery as the device moves into a higher pH environment when it leaves the stomach and enters the duodenum.
In FIG. 3, the device 10 is shown in a perspective view, with part of the housing 11 and the membrane 12 cut away in order to illustrate the structure of the device. Thus, it can be seen that the base of the housing is coated with silver chloride 17 in one region and with nickel 16 in another region. The conductors 18 and printed circuit 19 connecting the silver chloride and nickel electrodes are on the underside of the device 10 as it is viewed in FIG. 3 and accordingly cannot be seen.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3894538 *||Aug 6, 1973||Jul 15, 1975||Siemens Ag||Device for supplying medicines|
|US3996126 *||Oct 31, 1974||Dec 7, 1976||Rasmussen Oeystein||Means for removal of adsorbed film and microorganisms from teeth and oral cavities|
|US4036228 *||Sep 11, 1975||Jul 19, 1977||Alza Corporation||Osmotic dispenser with gas generating means|
|US4203439 *||Oct 11, 1978||May 20, 1980||Alza Corporation||Osmotic system with volume amplifier for increasing amount of agent delivered therefrom|
|US4203441 *||Dec 18, 1978||May 20, 1980||Alza Corporation||Osmotically triggered device with gas generating means|
|US4327725 *||Nov 25, 1980||May 4, 1982||Alza Corporation||Osmotic device with hydrogel driving member|
|US4331728 *||Dec 10, 1979||May 25, 1982||Alza Corporation||Laminate made of a cellulose acetate layer and an elastomeric material layer|
|US4344929 *||Jan 26, 1981||Aug 17, 1982||Alza Corporation||Method of delivering drug with aid of effervescent activity generated in environment of use|
|US4675174 *||Aug 16, 1985||Jun 23, 1987||Alza Corporation||Veterinary dispenser delivering beneficial agent by gas power generated in situ|
|US4765989 *||Sep 2, 1986||Aug 23, 1988||Alza Corporation||Osmotic device for administering certain drugs|
|US4783337 *||Sep 29, 1986||Nov 8, 1988||Alza Corporation||Osmotic system comprising plurality of members for dispensing drug|
|US4786500 *||Jun 26, 1986||Nov 22, 1988||Alza Corporation||Programmable agent delivery system|
|US4955881 *||Jul 25, 1989||Sep 11, 1990||Alza Corporation||Ruminant dispensing device|
|US5023076 *||Mar 26, 1990||Jun 11, 1991||Alza Corporation||Lamina comprising carboxyvinyl polymer|
|US5135499 *||Jul 12, 1990||Aug 4, 1992||Apcis||Device for delivering a pharmacologically active principle by electrolytic pumping|
|US5318557 *||Feb 22, 1993||Jun 7, 1994||Elan Medical Technologies Limited||Medication administering device|
|US5354264 *||Feb 17, 1993||Oct 11, 1994||Insutech, Inc.||Gas pressure driven infusion system by hydrogel electrolysis|
|US5358721 *||Dec 4, 1992||Oct 25, 1994||Alza Corporation||Antiviral therapy|
|FR2195461A1 *||Title not available|
|WO1991000753A1 *||Jul 12, 1990||Jan 24, 1991||Apcis||Device for releasing a pharmacologically active principle by electrolytic pumping|
|WO1994001165A1 *||Jul 9, 1993||Jan 20, 1994||Elan Med Tech||Medication administering device|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US6572740||Apr 11, 2001||Jun 3, 2003||Elan Pharma International Limited||Electrolytic cell|
|US6632175||Nov 8, 2000||Oct 14, 2003||Hewlett-Packard Development Company, L.P.||Swallowable data recorder capsule medical device|
|US6764472||Jan 11, 2000||Jul 20, 2004||Bard Access Systems, Inc.||Implantable refillable infusion device|
|US6776165 *||Sep 12, 2002||Aug 17, 2004||The Regents Of The University Of California||Magnetic navigation system for diagnosis, biopsy and drug delivery vehicles|
|US6800060||Sep 16, 2003||Oct 5, 2004||Hewlett-Packard Development Company, L.P.||Swallowable data recorder capsule medical device|
|US6929636||Nov 8, 2000||Aug 16, 2005||Hewlett-Packard Development Company, L.P.||Internal drug dispenser capsule medical device|
|US7160258||Jun 26, 2001||Jan 9, 2007||Entrack, Inc.||Capsule and method for treating or diagnosing the intestinal tract|
|US7452354||Jun 26, 2002||Nov 18, 2008||Inset Technologies Incorporated||Implantable pump connector for catheter attachment|
|US7458965||May 26, 2005||Dec 2, 2008||Microlin, Llc||Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method|
|US7470267||May 1, 2002||Dec 30, 2008||Microlin, Llc||Fluid delivery device having an electrochemical pump with an anionic exchange membrane and associated method|
|US7611480 *||Apr 24, 2003||Nov 3, 2009||Levy Mark M||Gastrointestinal bioreactor|
|US7658736||Feb 11, 2005||Feb 9, 2010||Hewlett-Packard Development Company, L.P.||Internal drug dispenser capsule medical device|
|US7785302||Mar 6, 2006||Aug 31, 2010||C. R. Bard, Inc.||Access port identification systems and methods|
|US7824347||May 1, 2003||Nov 2, 2010||Entrack, Inc.||System for marking a location for treatment within the gastrointestinal tract|
|US7896867||Jul 1, 2005||Mar 1, 2011||Microlin, Llc||Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method|
|US7927325||Dec 9, 2004||Apr 19, 2011||Medasys Incorporated||Implantable pump connector for catheter attachment|
|US7947022||Apr 7, 2009||May 24, 2011||C. R. Bard, Inc.||Access port identification systems and methods|
|US7959615||Jan 31, 2008||Jun 14, 2011||C. R. Bard, Inc.||Access port identification systems and methods|
|US7978064||Jul 12, 2011||Proteus Biomedical, Inc.||Communication system with partial power source|
|US8005536||Dec 22, 2003||Aug 23, 2011||Entrack, Inc.||Capsule and method for treating or diagnosing conditions or diseases of the intestinal tract|
|US8025639||Apr 7, 2009||Sep 27, 2011||C. R. Bard, Inc.||Methods of power injecting a fluid through an access port|
|US8029482||Jun 8, 2010||Oct 4, 2011||C. R. Bard, Inc.||Systems and methods for radiographically identifying an access port|
|US8036748||Nov 13, 2009||Oct 11, 2011||Proteus Biomedical, Inc.||Ingestible therapy activator system and method|
|US8054140||Oct 17, 2007||Nov 8, 2011||Proteus Biomedical, Inc.||Low voltage oscillator for medical devices|
|US8055334||Dec 10, 2009||Nov 8, 2011||Proteus Biomedical, Inc.||Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same|
|US8114021||Dec 15, 2009||Feb 14, 2012||Proteus Biomedical, Inc.||Body-associated receiver and method|
|US8115618||May 23, 2008||Feb 14, 2012||Proteus Biomedical, Inc.||RFID antenna for in-body device|
|US8177762||Dec 28, 2005||May 15, 2012||C. R. Bard, Inc.||Septum including at least one identifiable feature, access ports including same, and related methods|
|US8202259||Oct 30, 2009||Jun 19, 2012||C. R. Bard, Inc.||Systems and methods for identifying an access port|
|US8257325||Jun 20, 2008||Sep 4, 2012||Medical Components, Inc.||Venous access port with molded and/or radiopaque indicia|
|US8258962||Mar 5, 2009||Sep 4, 2012||Proteus Biomedical, Inc.||Multi-mode communication ingestible event markers and systems, and methods of using the same|
|US8301242||Feb 13, 2012||Oct 30, 2012||Cardiac Pacemakers, Inc.||Method and apparatus for a small power source for an implantable device|
|US8311627 *||Dec 13, 2010||Nov 13, 2012||Cardiac Pacemakers, Inc.||Method and apparatus for a small power source for an implantable device|
|US8348930||Mar 11, 2010||Jan 8, 2013||Microlin, Llc||Fluid delivery device with a diffusion membrane and electrochemical pump|
|US8360976||Jan 29, 2013||Entrack, Inc.||Optical capsule and spectroscopic method for treating or diagnosing the intestinal tract|
|US8382723||Jun 13, 2011||Feb 26, 2013||C. R. Bard, Inc.||Access port identification systems and methods|
|US8382724||Sep 30, 2011||Feb 26, 2013||C. R. Bard, Inc.||Systems and methods for radiographically identifying an access port|
|US8414559||May 7, 2009||Apr 9, 2013||Rainbow Medical Ltd.||Gastroretentive duodenal pill|
|US8475417||Apr 7, 2009||Jul 2, 2013||C. R. Bard, Inc.||Assemblies for identifying a power injectable access port|
|US8517961||Nov 1, 2010||Aug 27, 2013||Entrack, Inc.||System for marking a location for treatment within the gastrointestinal tract|
|US8532760||Nov 12, 2012||Sep 10, 2013||Cardiac Pacemakers, Inc.||Method and apparatus for a small power source for an implantable device|
|US8540632||May 23, 2008||Sep 24, 2013||Proteus Digital Health, Inc.||Low profile antenna for in body device|
|US8540633||Aug 13, 2009||Sep 24, 2013||Proteus Digital Health, Inc.||Identifier circuits for generating unique identifiable indicators and techniques for producing same|
|US8540664||Mar 24, 2010||Sep 24, 2013||Proteus Digital Health, Inc.||Probablistic pharmacokinetic and pharmacodynamic modeling|
|US8542123||Aug 1, 2012||Sep 24, 2013||Proteus Digital Health, Inc.||Multi-mode communication ingestible event markers and systems, and methods of using the same|
|US8545402||Apr 27, 2010||Oct 1, 2013||Proteus Digital Health, Inc.||Highly reliable ingestible event markers and methods for using the same|
|US8545436||Dec 23, 2011||Oct 1, 2013||Proteus Digital Health, Inc.||Body-associated receiver and method|
|US8545460||Apr 25, 2006||Oct 1, 2013||C. R. Bard, Inc.||Infusion apparatuses and related methods|
|US8547248||Sep 1, 2006||Oct 1, 2013||Proteus Digital Health, Inc.||Implantable zero-wire communications system|
|US8558563||Aug 23, 2010||Oct 15, 2013||Proteus Digital Health, Inc.||Apparatus and method for measuring biochemical parameters|
|US8583227||Sep 23, 2011||Nov 12, 2013||Proteus Digital Health, Inc.||Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same|
|US8585663||Mar 29, 2013||Nov 19, 2013||C. R. Bard, Inc.||Access port identification systems and methods|
|US8597186||Jan 5, 2010||Dec 3, 2013||Proteus Digital Health, Inc.||Pharmaceutical dosages delivery system|
|US8603052||Feb 25, 2013||Dec 10, 2013||C. R. Bard, Inc.||Access port identification systems and methods|
|US8608713||May 14, 2012||Dec 17, 2013||C. R. Bard, Inc.||Septum feature for identification of an access port|
|US8641676||Apr 3, 2012||Feb 4, 2014||C. R. Bard, Inc.||Infusion apparatuses and methods of use|
|US8641688||May 2, 2013||Feb 4, 2014||C. R. Bard, Inc.||Assemblies for identifying a power injectable access port|
|US8644922||Aug 5, 2013||Feb 4, 2014||Cardiac Pacemakers, Inc.||Method and apparatus for a small power source for an implantable device|
|US8674825||Mar 13, 2009||Mar 18, 2014||Proteus Digital Health, Inc.||Pharma-informatics system|
|US8715244||Jul 7, 2010||May 6, 2014||C. R. Bard, Inc.||Extensible internal bolster for a medical device|
|US8718193||Nov 19, 2007||May 6, 2014||Proteus Digital Health, Inc.||Active signal processing personal health signal receivers|
|US8721540||Nov 18, 2010||May 13, 2014||Proteus Digital Health, Inc.||Ingestible circuitry|
|US8730031||Jul 11, 2011||May 20, 2014||Proteus Digital Health, Inc.||Communication system using an implantable device|
|US8784308||Dec 2, 2010||Jul 22, 2014||Proteus Digital Health, Inc.||Integrated ingestible event marker system with pharmaceutical product|
|US8802183||Jul 11, 2011||Aug 12, 2014||Proteus Digital Health, Inc.||Communication system with enhanced partial power source and method of manufacturing same|
|US8805478||Apr 7, 2009||Aug 12, 2014||C. R. Bard, Inc.||Methods of performing a power injection procedure including identifying features of a subcutaneously implanted access port for delivery of contrast media|
|US8810409||May 6, 2013||Aug 19, 2014||Proteus Digital Health, Inc.||Multi-mode communication ingestible event markers and systems, and methods of using the same|
|US8816847||Jun 3, 2011||Aug 26, 2014||Proteus Digital Health, Inc.||Communication system with partial power source|
|US8836513||Jul 11, 2011||Sep 16, 2014||Proteus Digital Health, Inc.||Communication system incorporated in an ingestible product|
|US8847766||Apr 28, 2006||Sep 30, 2014||Proteus Digital Health, Inc.||Pharma-informatics system|
|US8852160||Jul 16, 2012||Oct 7, 2014||Medical Components, Inc.||Venous access port with molded and/or radiopaque indicia|
|US8858432||Feb 1, 2008||Oct 14, 2014||Proteus Digital Health, Inc.||Ingestible event marker systems|
|US8868453||Nov 4, 2010||Oct 21, 2014||Proteus Digital Health, Inc.||System for supply chain management|
|US8912908||Jul 11, 2011||Dec 16, 2014||Proteus Digital Health, Inc.||Communication system with remote activation|
|US8915867||Aug 26, 2013||Dec 23, 2014||Entrack, Inc.||System for marking a location for treatment within the gastrointestinal tract|
|US8932221||Mar 7, 2008||Jan 13, 2015||Proteus Digital Health, Inc.||In-body device having a multi-directional transmitter|
|US8932271||Nov 13, 2009||Jan 13, 2015||C. R. Bard, Inc.||Implantable medical devices including septum-based indicators|
|US8938293||Feb 3, 2014||Jan 20, 2015||Cardiac Pacemakers, Inc.||Method and apparatus for a small power source for an implantable device|
|US8939947||Feb 25, 2013||Jan 27, 2015||C. R. Bard, Inc.||Systems and methods for radiographically identifying an access port|
|US8945005||Oct 25, 2007||Feb 3, 2015||Proteus Digital Health, Inc.||Controlled activation ingestible identifier|
|US8956287||May 2, 2007||Feb 17, 2015||Proteus Digital Health, Inc.||Patient customized therapeutic regimens|
|US8956288||Feb 14, 2008||Feb 17, 2015||Proteus Digital Health, Inc.||In-body power source having high surface area electrode|
|US8961412||Sep 25, 2008||Feb 24, 2015||Proteus Digital Health, Inc.||In-body device with virtual dipole signal amplification|
|US8998860||Jun 15, 2012||Apr 7, 2015||C. R. Bard, Inc.||Systems and methods for identifying an access port|
|US9014779||Jan 28, 2011||Apr 21, 2015||Proteus Digital Health, Inc.||Data gathering system|
|US9060708||Jul 25, 2014||Jun 23, 2015||Proteus Digital Health, Inc.||Multi-mode communication ingestible event markers and systems, and methods of using the same|
|US9079004||Nov 1, 2010||Jul 14, 2015||C. R. Bard, Inc.||Overmolded access port including anchoring and identification features|
|US9083589||Mar 6, 2014||Jul 14, 2015||Proteus Digital Health, Inc.||Active signal processing personal health signal receivers|
|US9107806||Nov 18, 2011||Aug 18, 2015||Proteus Digital Health, Inc.||Ingestible device with pharmaceutical product|
|US9119554||Nov 18, 2010||Sep 1, 2015||Proteus Digital Health, Inc.||Pharma-informatics system|
|US9119918||May 8, 2013||Sep 1, 2015||Proteus Digital Health, Inc.||Probablistic pharmacokinetic and pharmacodynamic modeling|
|US9149423||May 10, 2010||Oct 6, 2015||Proteus Digital Health, Inc.||Ingestible event markers comprising an ingestible component|
|US9149577||Apr 30, 2013||Oct 6, 2015||Proteus Digital Health, Inc.||Body-associated receiver and method|
|US9161707||Sep 12, 2014||Oct 20, 2015||Proteus Digital Health, Inc.||Communication system incorporated in an ingestible product|
|US9167990||Dec 23, 2013||Oct 27, 2015||Entrack, Inc.||Optical capsule and spectroscopic method for treating and diagnosing the intestinal tract|
|US9198608||Nov 23, 2011||Dec 1, 2015||Proteus Digital Health, Inc.||Communication system incorporated in a container|
|US9235683||Nov 9, 2011||Jan 12, 2016||Proteus Digital Health, Inc.||Apparatus, system, and method for managing adherence to a regimen|
|US9248268||Aug 9, 2012||Feb 2, 2016||C. R. Bard, Inc.||Overmolded access port including anchoring and identification features|
|US20020198470 *||Jun 26, 2001||Dec 26, 2002||Imran Mir A.||Capsule and method for treating or diagnosing the intestinal tract|
|US20030205582 *||May 1, 2002||Nov 6, 2003||Joshi Ashok V.||Fluid delivery device having an electrochemical pump with an anionic exchange membrane and associated method|
|US20030208184 *||Jan 11, 2001||Nov 6, 2003||Paul Burke||Implantable, refillable infusion device and spetum replacement kit|
|US20040002693 *||Jun 26, 2002||Jan 1, 2004||Bright Jeffrey D.||Implantable pump connector for catheter attachment|
|US20040050394 *||Sep 12, 2002||Mar 18, 2004||Sungho Jin||Magnetic navigation system for diagnosis, biopsy and drug delivery vehicles|
|US20040059204 *||Sep 16, 2003||Mar 25, 2004||Marshall Daniel R.||Swallowable data recorder capsule medical device|
|US20040068204 *||May 1, 2003||Apr 8, 2004||Imran Mir A.||System for marking a location for treatment within the gastrointestinal tract|
|US20040162469 *||Dec 22, 2003||Aug 19, 2004||Imran Mir A.||Optical capsule and spectroscopic method for treating or diagnosing the intestinal tract|
|US20040162501 *||Dec 22, 2003||Aug 19, 2004||Imran Mir A.||Capsule and method for treating or diagnosing conditions or diseases of the intestinal tract|
|US20040253304 *||Jan 29, 2004||Dec 16, 2004||Yossi Gross||Active drug delivery in the gastrointestinal tract|
|US20040267240 *||May 3, 2004||Dec 30, 2004||Yossi Gross||Active drug delivery in the gastrointestinal tract|
|US20050058701 *||Jul 29, 2004||Mar 17, 2005||Yossi Gross||Active drug delivery in the gastrointestinal tract|
|US20050096635 *||Dec 9, 2004||May 5, 2005||Bright Jeffrey D.||Implantable pump connector for catheter attachment|
|US20050147559 *||Feb 11, 2005||Jul 7, 2005||Von Alten Thomas W.||Internal drug dispenser capsule medical device|
|US20050242579 *||Jun 26, 2003||Nov 3, 2005||Bright Jeffrey D||Connector for catheter attachment to an implantable pump|
|US20060052768 *||May 26, 2005||Mar 9, 2006||Microlin, L.C.||Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method|
|US20060116641 *||Jul 1, 2005||Jun 1, 2006||Microlin, L.C.|
|US20060116663 *||Jul 1, 2005||Jun 1, 2006||Joshi Ashok V||Electro-osmotic fluid delivery device and method|
|US20060145876 *||Feb 24, 2006||Jul 6, 2006||Fujitsu Limited||Medicine ingestion state management method, medicine and medicine ingestion state management device|
|US20060276844 *||May 18, 2006||Dec 7, 2006||Ruth Alon||Ingestible device for nitric oxide production in tissue|
|US20070021734 *||Jul 12, 2006||Jan 25, 2007||Sai Bhavaraju||Bioelectro-osmotic engine fluid delivery device|
|US20080015523 *||Jul 19, 2007||Jan 17, 2008||Sentinel Group, Llc||Medical agent delivery system and method|
|US20080188837 *||Dec 14, 2005||Aug 7, 2008||Ziv Belsky||Local Delivery of Drugs or Substances Using Electronic Permeability Increase|
|US20100214033 *||Oct 17, 2007||Aug 26, 2010||Robert Fleming||Low voltage oscillator for medical devices|
|US20100222770 *||Mar 11, 2010||Sep 2, 2010||John Howard Gordon||Fluid delivery device with a diffusion membrane for fast response time|
|US20100286587 *||May 7, 2009||Nov 11, 2010||Yossi Gross||Sublingual electrical drug delivery|
|US20100312228 *||Nov 13, 2009||Dec 9, 2010||Mark Zdeblick||Ingestible therapy activator system and method|
|US20110040203 *||Dec 10, 2009||Feb 17, 2011||George Savage||Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same|
|US20110046479 *||Nov 1, 2010||Feb 24, 2011||Imran Mir A||System for marking a location for treatment within the gastrointestinal tract|
|US20110066175 *||Nov 5, 2010||Mar 17, 2011||Rainbow Medical Ltd.||Gastric anchor|
|US20110082509 *||Dec 13, 2010||Apr 7, 2011||Root Michael J||Method and apparatus for a small power source for an implantable device|
|USD676955||Dec 30, 2010||Feb 26, 2013||C. R. Bard, Inc.||Implantable access port|
|USD682416||Dec 30, 2010||May 14, 2013||C. R. Bard, Inc.||Implantable access port|
|CN102379684B *||Apr 28, 2006||Nov 19, 2014||普罗透斯数字保健公司||Pharma-informatics system|
|CN102458236B *||Apr 27, 2010||Jan 27, 2016||普罗秋斯数字健康公司||高可靠性的可摄入事件标记器及其使用方法|
|WO2001079706A2 *||Apr 12, 2001||Oct 25, 2001||Elan Pharma Int Ltd||Electrolytic cell|
|WO2002095341A1||May 17, 2002||Nov 28, 2002||Durect Corp||Fluid delivery device having a water generating electrochemical/chemical pump and associated method|
|WO2006064502A2 *||Dec 14, 2005||Jun 22, 2006||Pill Pharma Ltd E||Local delivery of drugs or substances using electronic permeability increase|
|WO2006116718A2 *||Apr 28, 2006||Nov 2, 2006||Proteus Biomedical Inc||Pharma-informatics system|
|U.S. Classification||604/890.1, 604/891.1, 604/141|
|International Classification||A61M31/00, A61M5/142, A61K9/00, A61K9/22, A61M5/145|
|Cooperative Classification||A61M5/14593, A61M2005/14204, A61M31/002, A61K9/0009|
|European Classification||A61K9/00L8, A61M5/145D2, A61M31/00D|
|Jan 29, 1999||AS||Assignment|
Owner name: ELAN CORPORATION, PLC, IRELAND
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ELAN MEDICAL TECHNOLOGIES LIMITED;REEL/FRAME:009719/0946
Effective date: 19981210
|Feb 5, 2003||REMI||Maintenance fee reminder mailed|
|Jul 21, 2003||LAPS||Lapse for failure to pay maintenance fees|
|Sep 16, 2003||FP||Expired due to failure to pay maintenance fee|
Effective date: 20030720
|Jul 6, 2010||AS||Assignment|
Owner name: ELAN PHARMA INTERNATIONAL LIMITED, IRELAND
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ELAN CORPORATION, PLC;REEL/FRAME:024640/0053
Effective date: 20061231